To examine the safety and effectiveness of mupirocin in eradicating colonization with SA (MRSA or MSSA) and preventing the occurrence of invasive and other clinically significant SA infections among infants in the ICU. To evaluate the safety and clinical acceptability of a 5-day course (15 applications) of topical mupirocin applied every 8 hours (+/= 2 hours) daily to the nares, umbilicus and perianal area of infants residing in the ICU. Infants less than 24 months of age will be recruited from among those admitted to the NICU or ICU at one of the participating centers. Study duration is 36 months. Enrolled infants will continue to receive medical care as they otherwise would if they were not enrolled in the trial. The study will be powered toward the primary endpoint with 126 participants. Enrollment may continue up to a maximum of 500 participants to inform the secondary and exploratory endpoints and to help design any subsequent study.

Persistent decolonization efficacy: Proportion of infants in the treatment and control groups who have no detectable SA on direct cultures on days 8 and 22 [ Time Frame: Days 8 and 22 ] [ Designated as safety issue: No ]

Primary decolonization efficacy: Proportion of infants in the treatment and control groups who have no detectable S. aureus (SA) on direct cultures obtained on day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To measure the time until decolonization: Time from Day 1 until the first NUP collection with no SA is detected in the nares, umbilical, and perianal areas [ Time Frame: Day 1 through 85 ] [ Designated as safety issue: No ]

Protective efficacy of clinical SA infection in the treatment compared to the control group during days 1-22 or until discharge, whichever occurs first. [ Time Frame: Days 1 through 22 ] [ Designated as safety issue: No ]

Mupirocin calcium ointment 2% will be applied intranasally every 8 hours for 5 days, for a total of 15 applications

Drug: Mupirocin calcium

Mupirocin calcium cream 2% applied topically to umbilicus and perianal area every 8 hours for 5 days, for a total of 15 applications

Detailed Description:

This is a Phase 2, open label, multi-center, randomized trial to determine the safety and efficacy of mupirocin in eradicating colonization with Staphylococcus aureus (SA) and preventing the occurrence of invasive and other clinically significant SA infections among critically ill infants in the ICU. Infants hospitalized in an ICU at any one of the 6 participating centers with a positive nasal culture for SA will be eligible to enroll. Infants will be stratified by birth gestational age (< 28 weeks and <8 weeks of post-natal life or >/= 28 weeks / < 28 weeks and >/=8 weeks of post-natal life) and colonizing strain Methicillin-resistant Staphylococcus aureus (MRSA) or Methicillin-sensitive Staphylococcus aureus (MSSA) and then randomized 1:1 to receive a 5 day course of mupirocin applied to the nares, umbilicus and perianal (NUP) areas every 8 hours (+/= 2 hours) vs. no treatment. (Stratification by birth gestational age is performed to minimize bias that could result from a higher risk for developing infection due to prematurity or prolonged length of stay due to prematurity.) Each participant will be enrolled for up to 12 weeks (Day 85) or until the time of discharge from the hospital, death or withdrawal from further participation, whichever occurs first. It is anticipated that it will take at least 2 years to enroll all participants. Study duration is 36 months. Enrolled infants will continue to receive medical care as they otherwise would if they were not enrolled in the trial. The study will be powered toward the primary endpoint with 126 participants. Enrollment may continue up to a maximum of 500 participants to inform the secondary and exploratory endpoints and to help design any subsequent study.

Eligibility

Ages Eligible for Study:

up to 24 Months

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Currently admitted to a NICU or ICU at a participating site

Chronological age less than 24 months

Evidence of colonization with SA (MRSA or MSSA) based on a positive nasal surveillance culture. Randomization must occur within 7 days (168 hours) of receipt of the nasal surveillance swab by the laboratory

The attending neonatologist/ intensivist anticipates that the infant will remain in the ICU for a minimum of 14 days after enrollment

Parent or legal guardian agrees that the infant will not participate in a research trial involving the administration of an investigational drug for 14 days following enrollment

Exclusion Criteria:

Receipt of an investigational drug as part of a research trial within the past 14 days

Previously enrolled and participated in this trial

Has an active or previous SA infection or previous SA colonization

Currently receiving topical or intranasal mupirocin

Has a rash in an area to which mupirocin will be directly applied

Has any of the following congenital abnormalities:

A congenital skin disorder (i.e. - epidermolysis bullosa, icthyosis)

An opened neural tube defect

Confirmed or suspected choanal atresia

Any of the following abdominal wall defects: wound dehiscence, gastroschisis, open abdominal wound (small abdominal wall defects such as ostomy sites or peritoneal drain sites are not exclusionary)

Is nasally intubated

Known hypersensitivity to the trial product or its constituents

Known or suspected immune deficiency. Infants born to HIV-seropositive mothers with the following risk factors for intrapartum transmission will not be eligible to participate:

Mother's most recent viral load within the past 3 months was > 1,000 copies/ml or

Mother's viral load is not known or has has not been measured in the past 3 months.

Any other condition(s) that in the opinion of the investigator would jeopardize the safety or rights of a participant or would render the participant unable to comply with the protocol

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01827358